<p>Osteoarthritis is a common degenerative disease; once the joints are damaged, they cannot be healed, which seriously affects the quality of life of patients. For early osteoarthritis, hyaluronic acid (HA) is injected into the joint cavity to relieve pain, and oral medication is used to reduce inflammation, but studies have shown that HA has a short duration of action and the utilisation rate of oral medication is low. We mimic the hydration lubrication function of natural lubricin by grafting HA onto chitosan-loaded nanospheres and using the polar groups on the HA molecular chain to adsorb water molecules and form a hydration shell around the nanospheres. The friction behaviour of natural cartilage and artificial joint surfaces showed that our prepared HA-coated chitosan-loaded nanospheres have a certain lubrication function, which is mainly because the chitosan nanospheres change the sliding friction of the friction interface into rolling friction, greatly reducing the contact surface friction, and the hydrated shells adsorbed by the HA also play the role of hydration lubrication. In vitro drug release studies showed that the HA-coated chitosan-loaded nanospheres had drug-carrying and releasing capacity, with a drug release rate of up to 85.8% at 72h. In addition, in vitro haemolysis experiments showed that the nanospheres have very high blood compatibility. The synthesis of this highly biocompatible multifunctional material with both lubrication function and drug release effect provides a new strategy for the treatment of early osteoarthritis.</p> Graphical Abstract